Traumatic brain injury (TBI) produces several cellular changes, such as gliosis, axonal and dendritic plasticity, and inhibition-excitation imbalance, as well as cell death, which can initiate epileptogenesis. It has been demonstrated that dysfunction of the inhibitory components of the cerebral cortex after injury may cause status epilepticus in experimental models; we proposed to analyze the response of cortical interneurons and astrocytes after TBI in humans. Twelve contusion samples were evaluated, identifying the expression of glial fibrillary acidic protein (GFAP) and calcium-binding proteins (CaBPs). The study was made in sectors with and without preserved cytoarchitecture evaluated with NeuN immunoreactivity (IR). In sectors with total loss of NeuN-IR the results showed a remarkable loss of CaBP-IR both in neuropil and somata. In sectors with conserved cytoarchitecture less drastic changes in CaBP-IR were detected. These changes include a decrease in the amount of parvalbumin (PV-IR) neurons in layer II, an increase of calbindin (CB-IR) neurons in layers III and V, and an increase in calretinin (CR-IR) neurons in layer II. We also observed glial fibrillary acidic protein immunoreactivity (GFAP-IR) in the white matter, in the gray-white matter transition, and around the sectors with NeuN-IR total loss. These findings may reflect dynamic activity as a consequence of the lesion that is associated with changes in the excitatory circuits of neighboring hyperactivated glutamatergic neurons, possibly due to the primary impact, or secondary events such as hypoxia-ischemia. Temporal evolution of these changes may be the substrate linking severe cortical contusion and the resulting epileptogenic activity observed in some patients.

The von Economo neurons (VEN) are characterized by a large soma, spindle-like soma, with little dendritic arborization at both, the basal and apical poles. In humans, VENs have been described in the entorhinal cortex, the hippocampal formation, the anterior cingulate cortex, the rostral portion of the insula and the dorsomedial Brodmann’s area 9 (BA9). These cortical regions have been associated with cognitive functions such as social interactions, intuition and emotional processing. Previous studies that searched for the presence of these cells in the lateral frontal poles yielded negative results. The presence of VENs in other cortical areas on the medial surface of the human prefrontal cortex which share both a common functional network and similar laminar organization, led us to examine its presence in the medial portion of the frontal pole. In the present study, we used tissue samples from five postmortem subjects taken from the polar portion of BA10, on the medial surface of both hemispheres. We found VENs in the human medial BA10, although they are very scarce and dispersed. We also observed crests and walls of the gyrus to quantitatively assess: (A) interhemispheric asymmetries, (B) the VENs/pyramidal ratio, (C) the area of the soma of VENs and (D) the difference in soma area between VENs and pyramidal and fusiform cells. We found that VENs are at least seven times more abundant on the right hemisphere and at least 2.5 times more abundant in the crest than in the walls of the gyrus. The soma size of VENs in the medial frontopolar cortex is larger than that of pyramidal and fusiform cells of layer VI, and their size is larger in the walls than in the crests. Our finding might be a contribution to the understanding of the role of these neurons in the functional networks in which all the areas in which they have been found are linked. However, the particularities of VENs in the frontal pole, as their size and quantity, may also lead us to interpret the findings in the light of other positions such as van Essen’s theory of tension-based brain morphogenesis.

Early life stress can be caused by acute or chronic exposure to childhood events, such as emotional, physical, sexual abuse, and neglect. Early stress is associated with subsequent alterations in physical and mental health, which can extend into adolescence, adulthood, and even old age. The effects of early stress exposure include alterations in cognitive, neuropsychological, and behavioral functions, and can even lead to the development of psychiatric disorders and changes in brain anatomy. The present manuscript provides a review of the main findings on these effects reported in the scientific literature in recent decades. Early life stress is associated with the presence of psychiatric disorders, mainly mood disorders such as depression and risk of suicide, as well as with the presence of post-traumatic stress disorder. At the neuropsychological level, the involvement of different mental processes such as executive functions, abstract reasoning, certain memory modalities, and poor school-skill performance has been reported. In addition, we identified reports of alterations of different subdomains of each of these processes. Regarding neuroanatomical effects, the involvement of cortical regions, subcortical nuclei, and the subcortical white matter has been documented. Among the telencephalic regions most affected and studied are the prefrontal cortex, the hippocampus, the amygdala, and the anterior cingulate cortex. Understanding the impact of early life stress on postnatal brain development is very important for the orientation of therapeutic intervention programs and could help in the formulation and implementation of preventive measures as well as in the reorientation of research targets.

Neuroinflammation plays a pivotal role in the onset and progression of epilepsy. In this review, we critically examine: (1) the dual roles of astrocytes and microglia in maintaining a chronic inflammation and its contribution to epileptogenesis and seizures; (2) the crosstalk between the histamine released by mast cells and the brain histaminergic neurotransmission, an underexplored mechanism for seizures; (3) the potential of inflammatory mediators as biomarkers for predicting prognosis and risk stratification; (4) the shared inflammatory pathways linking epilepsy and Alzheimer's disease, with special attention to reactive astrocyte and ferroptosis markers in identifying individuals at risk; (5) emerging therapeutic strategies, including conventional anti-inflammatory drugs and traditional medicine, for seizure control through modulation of neuroinflammation. With these carefully chosen topics, we introduce new molecular findings reinforcing the crucial role of neuroinflammation in epilepsy and as a marker for epileptogenesis, a topic of special interest for the acquired epilepsies such as hippocampal sclerosis. Moreover, we explored other mechanisms that received far less attention, especially those linking epilepsy with Alzheimer's disease, and the potential role of mast cells in seizures.

The pathophysiology of traumatic brain injury (TBI) has not yet been fully elucidated. Crystallin alpha-B (CRYAB) is a molecular chaperone that apparently tries to stabilize the rapid thickening of the intermediate filaments of glial fibrillary acidic protein (GFAP) during the process of reactive astrogliosis in response to TBI. Previous analyses of the gene expression profile in human brain contusion tissue showed us an exacerbated CRYAB overexpression. Here, we used 3, 3’-diaminobenzidine (DAB) immunohistochemistry and immunofluorescence to verify CRYAB overexpression and to describe its expression and distribution in samples of contused cortical tissue derived from emergency decompressive surgery after severe TBI. The histological expression of CRYAB was mainly seen in subcortical white matter astrocytes of injured tissue. Most of the cells that overexpressed GFAP in the analyzed tissue also overexpressed CRYAB, a finding corroborated by the co-localization of the two markers. The only difference was the presence of a few pyramidal neurons that expressed CRYAB in layer V of the cerebral cortex. The selective vulnerability of layer V of the cerebral cortex during TBI could explain the expression of CRYAB in neurons of this cortical layer. Our results indicate a parallel behavior in the cellular expression of CRYAB and GFAP during the subacute response to TBI. These results lead us to postulate CRYAB as a possible marker of reactive astrogliosis in contused cortical tissue.